Interstate 5 (the Grapevine) is the most direct, flatest route between Northern and Southern California. It's the one the truck drivers use.

It's, for the most part, featureless and dull. There's a steep pass just south of Bakersfield, but that's about it. You take the 5 until Sacramento, then you take the 80.

The 395, on the otherhand, is a beautiful highway taking you passed the beautiful Eastern Sierras, including the Mount Whitney portal. It also has some stops of interest like Manzanar (the camp where the US interred the Japanese during WW2.) The trade-off is that 395, at least past Mammoth Lakes, gets very steep. And it's more circuitous than Interstate 5.